Abstract |
Transforming growth factor-beta receptor (TbetaR)-dependent signals are critical for cell growth and differentiation and are often disrupted during tumorigenesis. The entire coding region of TbetaR-I and flanking intron sequences from 30 head and neck carcinomas were examined for alterations using "Cold" SSCP and direct sequencing. No somatic point mutations were found in the TbetaR-I gene. In contrast, 14 polymorphic sequence changes were detected in TbetaR-I in 13 (43%) of the samples, including eight (27%) nucleotide alterations identified as polymorphisms in an exon-1 (GCG)(9) microsatellite repeat, a previously reported tumor susceptibility allele. A nine base pair deletion was found in 23% of the samples including five heterozygous and two homozygous deletions as well as single homozygous 12bp deletion. Additionally, six heterozygous polymorphisms in intronic sequences were determined, including one heterozygous C/A genotype at the +82 nucleotide position of the intron-5 intervening sequence (IVS), and five heterozygous G/A genotypes within intron-7 at the +24 nucleotide position. Exon-1 polymorphisms in the (GCG)(9) microsatellite region of the TbetaR-I gene and their association with head/ neck cancers, suggest that development of these cancers may be a direct consequence of loss of responsiveness to TGF-beta mediated growth inhibition.
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Authors | T J Knobloch, M A Lynch, H Song, V L DeGroff, B C Casto, E M Adams, K Y Alam, J C Lang, D E Schuller, C M Weghorst |
Journal | Mutation research
(Mutat Res)
Vol. 479
Issue 1-2
Pg. 131-9
(Aug 08 2001)
ISSN: 0027-5107 [Print] Netherlands |
PMID | 11470488
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Receptors, Transforming Growth Factor beta
- Protein Serine-Threonine Kinases
- Activin Receptors, Type I
- Receptor, Transforming Growth Factor-beta Type I
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Topics |
- Activin Receptors, Type I
(genetics)
- Alleles
- Carcinoma, Squamous Cell
(genetics)
- DNA Mutational Analysis
- Exons
- Gene Deletion
- Genetic Predisposition to Disease
- Genotype
- Head and Neck Neoplasms
(genetics)
- Heterozygote
- Homozygote
- Humans
- Introns
- Microsatellite Repeats
- Mutation
- Phenotype
- Polymerase Chain Reaction
- Polymorphism, Genetic
- Polymorphism, Single-Stranded Conformational
- Protein Serine-Threonine Kinases
- Receptor, Transforming Growth Factor-beta Type I
- Receptors, Transforming Growth Factor beta
(genetics)
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